Alterations in plasma pharmacokinetics of cisplatin in tumor-bearing rats

Rats were inoculated s.c. with the Walker 256 solid carcinosarcoma, and when tumors reached a weight of approximately 2-3 g, pharmacokinetics, tissue distribution, and urinary excretion of 195mPt-labelled cisplatin were studied. Cisplatin was given i.v., blood was sampled through arterial cannulae, and data were fitted to a three-compartment model. Distribution half-times were prolonged two- to threefold in tumor-bearing animals, although there was no change in elimination half-time. Initial and steady-state volumes of distribution were also increased in tumor-bearing animals. There was no change in AUC, urinary excretion, tissue distribution, or plasma protein binding. The results indicate that a solid tumor represents an additional compartment for distribution of cisplatin and alters the rate at which cisplatin is distributed from the plasma.